Chronic Myeloid Leukemia: Mechanisms of Resistance and Treatment

Imatinib mesylate has revolutionized the treatment landscape for patients with newly diagnosed chronic myeloid leukemia (CML). Imatinib at a dose of 400 mg/day is considered the standard treatment for all newly diagnosed chronic phase CML. Follow-up on the pivotal International Randomized Study of Interfreron versus STI571 (IRIS) study has shown excellent response rates, progression-free survival and overall survival after 8 years of follow-up. However, some patients will develop resistance to imatinib treatment due to a multitude of reasons. Numerous strategies to overcome resistance are available including dose escalation of imatinib, switching to a second generation tyrosine kinase inhibitor or to one of the newer non-tyrosine kinase inhibitors. This review guides the treating physician with a rational approach in the management of CML patients who fail initial treatment with imatinib or lose response while on therapy with imatinib.